Glucose-6-phosphate Isomerase (GPI)

Glucose-6-phosphate isomerase (GPI) is an enzyme that catalyzes the reversible interconversion of D-glucose-6-phosphate and D-fructose-6-phosphate, a critical step in glycolysis and gluconeogenesis. Beyond its metabolic function, GPI exhibits moonlighting activities, acting as an angiogenic factor, neuroleukin (a neurotrophic factor), and autocrine motility factor promoting cancer cell metastasis. Mutations in GPI can cause glucose phosphate isomerase deficiency, leading to hemolytic anemia and neurological symptoms. In cancer, its overexpression/secretion promotes tumor metastasis.

Other names

Phosphoglucose isomerasePhosphohexose isomeraseAutocrine motility factorAMFNeuroleukinNLKSperm antigen 36SA-36

Acid/base catalysis: His388 protonates the C5 oxygen; Lys518 deprotonates C1 hydroxyl to open glucose’s ring structure. Substrate rotates about C3-C4; Glu357 abstracts a proton from C2 forming a cis-enediol intermediate stabilized by Arg272. Proton transfer completes conversion to fructose 6-phosphate; substrate ring closes via further rotation and deprotonation by Lys518.